– AGORA

In renal transplantation, monitoring the risk of subclinical rejection (SCR) and graft failure remains challenging. AGORA partners developed and validated 1-year non-invasive biomarkers allowing the prediction of patients at high/low risk of subclinical rejection and graft failure: 1) the cSOT gene score and 2) donor-reactive memory B cells (mBC) to diagnose sub-clinical rejection, 3) the Kidney Transplant Failure Score (KTFS) and 4) the frequency of circulating TEMRA cells to stratify patients with a higher risk of immunological graft failure. The objectives of AGORA are thus to build an European non-invasive clinical decision-making tool for immunological risk stratification of graft failure through: 1) a retrospective study to validate our decision AGORA algorithm on an existing biocollection of 300 patients, and 2) according to the AGORA algorithm, a multicenter randomized open label trial of immunosuppression minimization AGORAC (extra-low Tacrolimus (TAC) vs standard of care) with stringent monitoring of TAC pharmacokinetics using finger-prick test. Economic efficiency of our new strategy will be evaluated during the multicenter randomized open label trial. We will integrate users’ perspectives by performing sociological interviews to promote the active involvement of patients in their clinical care and help clinicians for decision-making. Ancillary functional studies will reinforce the AGORA algorithm to assess immunological events following immunosuppression minimization. AGORA will be possible thanks to the collaboration of 4 European partners, internationally recognized in kidney transplantation and immunology, and who share previous experiences in collaboration. All the steps and biomarkers have already been validated by the 4 partners. AGORA could impact health care pathway for kidney transplant recipients by incorporating a medical decision tool, validated through European large studies for personalizing immunosuppressive therapy.